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Biomedical subjects

H Y Yap

Publications and source records attributed to H Y Yap.

At least 19 recordsLinked to original sources

Ethical attitudes of intensive care physicians in Hong Kong: questionnaire survey.

OBJECTIVES: To examine the practice and ethical attitudes of intensive care doctors in Hong Kong and to compare findings with those from European studies. DESIGN: Structured questionnaire survey, modified from a similar questionnaire used in Europe. SETTING: Eleven publicly funded intensive care units in Hong Kong. PARTICIPANTS: Ninety-five doctors practising in intensive care units. RESULTS: Of the sixty-five respondents, sizeable proportions indicated that the admission of patients to the intensive care unit is often (25%) or sometimes (51%) limited by bed availability. About 69% to 86% of doctors admit patients with limited prognosis or poor quality of life, although all felt that these admissions should be more restricted. 'Do-not-resuscitate' orders are applied by almost all respondents, and 52% and 89% of respondents would discuss such orders with the patient or with the family, respectively. The withholding and withdrawal of therapy from patients with no chance of recovery to a meaningful life is common in Hong Kong (99% and 89%, respectively). A total of 83% respondents involved patients or families in the decision to limit therapy, compared with less than half in Europe overall. When the family wanted aggressive life-support despite doctors' recommendations to limit therapy, 62% of the respondents would still withhold therapy while only 9% would withdraw therapy. More than 60% of doctors feel comfortable talking to patients' relatives about limitation of therapy. Approximately 75% felt that euthanasia is unacceptable. Most respondents (94%) reported that medical programmes should include more extensive discussion on ethical issues. CONCLUSION: The ethical attitudes of intensive care doctors in Hong Kong are similar to those of counterparts in Europe. However, Hong Kong doctors tend to involve families more often in the discussion of end-of-life issues.

Adult↗

Chemotherapy-induced neutropenia and fever in patients with metastatic breast carcinoma receiving salvage chemotherapy.

BACKGROUND: Chemotherapy-induced neutropenia and associated fever and infection are the most common complications of systemic chemotherapy. In this retrospective analysis, the authors evaluated the incidence of neutropenic fever, infection, and mortality in relation to the level of neutropenia, performance status, course number of chemotherapy, bone marrow metastasis, and age among patients with metastatic breast carcinoma receiving salvage chemotherapy. METHODS: A total of 174 patients with previously treated metastatic breast carcinoma enrolled on 4 consecutive Phase II protocols were evaluated. RESULTS: Twenty-three percent of the patients had an episode of neutropenic fever (41 episodes among 40 patients). The incidence of neutropenic fever did not increase until the absolute neutrophil count (ANC) had decreased to less than 500/microL, and then fever incidence had a linear relationship with decreasing ANC (linear trend, P < 0.01). A source of infection was documented in 59% of the neutropenic fever episodes. The incidence of infection did not increase significantly until the ANC had decreased to less than 250/microL (P < 0.01). The risk of neutropenic fever and infection was also significantly higher when patients had poor performance status or were undergoing the initial courses of chemotherapy. Patients with bone marrow metastases also had a higher frequency of fever, infection, and death, but these differences were not statistically significant. CONCLUSIONS: For patients with metastatic breast carcinoma receiving salvage chemotherapy, the risk of fever increases with decreasing ANC, but the risk of infection does not increase significantly until ANC decreases to less than 250/microL. Poor performance status, initial courses of chemotherapy, and bone marrow metastases further increase the risk of fever, infection, and death.

Adult↗

A comparative study of doxorubicin and epirubicin in patients with metastatic breast cancer.

Seventy-seven patients with progressive metastatic breast cancer refractory to prior therapy participated in a prospective randomized trial designed to compare the efficacy and toxicity of doxorubicin and epirubicin administered as single agents. In arm 1, 60 mg/m2 of doxorubicin and, in arm 2, 90 mg/m2 of epirubicin were administered by 48-h continuous i.v. infusion every 3 weeks. In arm 3, 90 mg/m2 of epirubicin was administered by bolus every 3 weeks. Patients in the three groups had similar characteristics, except that in arm 3 more patients were premenopausal, had more extensive disease, and fewer patients had been exposed to doxorubicin. Objective remission rates were 29, 26, and 13%, respectively for the three arms. Median response durations ranged from 4-6 months. No significant differences occurred in response rate, remission duration, or survival among patients in the three arms. The incidence of gastrointestinal toxicity and alopecia was evenly distributed. Hematologic toxicity was more severe in arms 2 and 3, and there was a higher incidence of infectious complications in arms 2 and 3 compared to arm 1 (p = 0.05). Two episodes of congestive heart failure occurred in arm 1, one in arm 2, and three in arm 3. Although the total cumulative anthracycline dosage was highest in the arm 2 group, they had the lowest incidence of cardiac toxicity. Epirubicin by bolus and doxorubicin administered by continuous infusion have similar potential for cardiac toxicity. Epirubicin administered by continuous infusion appears less cardiotoxic than doxorubicin by either method of administration or epirubicin given by bolus. Epirubicin appears equally active and less cardiotoxic than the parent compound doxorubicin in patients with metastatic breast cancer.

Adult↗

Chemotherapy with mitoxantrone in combination with continuous infusion vinblastine for metastatic breast cancer.

The efficacy of mitoxantrone in combination with vinblastine was assessed in 156 patients with metastatic breast cancer who had been treated previously with one or multiple chemotherapeutic regimens. Mitoxantrone was given by random assignment, either as a 10 mg/m2 single intravenous dose or in five consecutive daily fractions of 2 mg¿2. Vinblastine was given as a continuous intravenous infusion of 1.2 mg/m2 daily for 5 days. In 115 evaluable patients previously treated with doxorubicin, 21 objective responses (18%) and 11 minor responses (10%) were observed with similar distribution in the two treatment groups. Median time to progression was 27 weeks and 23 weeks, respectively. Eight (32%) of 25 patients who had not received doxorubicin achieved objective remissions and two (8%) had minor responses. Toxic effects were similar for the two treatment schedules. Major toxicities were myelosuppression and neutropenic fever. Other toxicities were mild. Cardiotoxicity, presumably caused by mitoxantrone, occurred in four patients. The combination of mitoxantrone and vinblastine appeared to offer no advantage over single-agent therapy, probably because of the dosage reduction required by the overlapping myelosuppressive toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Mitoxantrone, cyclophosphamide, and fluorouracil in metastatic breast cancer unresponsive to hormonal therapy.

Fifty-two patients with hormonally unresponsive or estrogen receptor negative metastatic breast cancer who had not received prior chemotherapy received mitoxantrone 10 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 1000 mg/m2 (MCF) by short intravenous infusion every 21 days. Disease that was resistant or stable to this regimen was treated with doxorubicin 25 mg/m2/day for two days and vinblastine 1.4 mg/m2/day for four days (DV). Both drugs were given by continuous infusion. Thirty-one partial remissions and four complete remissions occurred after treatment with MCF. Only thirty-four evaluable patients crossed to the DV phase with partial remission (11 patients), stable (five patients), or resistant (18 patients) disease. Eleven patients' responses were upgraded. The median overall time to progression (TTP), defined as the sum of the TTP on MCF and TTP on DV, was 12 months. The median survival of all patients was 19 months. Granulocytopenia was the dose limiting toxicity for MCF, but cumulative thrombocytopenia was noted. Nausea and vomiting occurred in most patients but was mild. Severe alopecia occurred in half the patients. One patient developed congestive heart failure after receiving a cumulative dose of 206 mg/m2 of mitoxantrone. The incidence of infectious complications was 35% on each regimen; 50% of these were mild. MCF is an effective combination that was well tolerated. Objective responses, durations of response, and survival were similar, but not superior, to standard doxorubicin-based combinations. Toxicity was somewhat less.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose induction chemotherapy of metastatic breast cancer in protected environment: a prospective randomized study.

To test the hypothesis of whether high doses of chemotherapy in combination achieve higher response rates and longer durations of response and survival, we treated 33 pre- and perimenopausal patients with good performance status in a prospective trial with escalating doses of fluorouracil, doxorubicin and cyclophosphamide (FAC). Patients were randomly assigned to be treated within a protected environment (laminar air flow room), with prophylactic antibiotics, or in a standard hospital room. Important patient characteristics were equally distributed in the two treatment arms. A major objective response was observed in 27 of the 32 evaluable patients (84%), and 11 (34%) achieved a complete remission (CR). There was no significant difference in overall and complete response rates between the two treatment arms, nor was there a substantial difference in times to progression or survival between the groups treated in or out of the protected environment. Comparison of the results of this study with previously reported programs of FAC chemotherapy in patients with metastatic breast cancer shows that this study achieved higher overall and complete response rates. However, neither the time to progression, nor the survival of responders or the entire patient group was different from our previous experience with standard FAC chemotherapy. When the study was initiated in 1976, the proposed dose escalation represented high-dose chemotherapy. In retrospect, even the "high" doses used in this study represent only a modest increase over standard doses of chemotherapy. Much steeper dose escalations will be needed to evaluate the efficacy of high-dose chemotherapy in breast cancer, as well as the protective value of the protected environment and prophylactic antibiotics in metastatic breast cancer.

Adult↗

Evaluation of high-dose versus standard FAC chemotherapy for advanced breast cancer in protected environment units: a prospective randomized study.

Fifty-nine evaluable patients under 65 years of age with measurable metastatic breast cancer and without prior chemotherapy were randomly assigned to treatment with fluorouracil, Adriamycin (Adria Laboratories, Columbus, OH), and cyclophosphamide (FAC) at standard or high doses (100% to 260% higher than standard FAC) following a dose escalation schedule. Patients randomized to the high-dose FAC received the first three cycles of therapy within a protected environment. Subsequent cycles for this group were administered at standard doses of FAC in an ambulatory setting, the same as for the control group. After reaching 450 mg/m2 of Adriamycin, patients in both groups continued treatment with cyclophosphamide, methotrexate, and fluorouracil until there was disease progression. Analysis of pretreatment patient characteristics showed an even distribution for most known pretreatment factors, although the control group had slightly (but nonsignificantly) more favorable prognostic characteristics. Fourteen patients (24%) achieved a complete remission (CR) and 32 (54%) achieved a partial remission (PR), for an overall major response rate of 78%. There were no differences in overall, CR, or PR rates between the high-dose FAC and control groups. The median response durations were 11 and 10 months for the protected environment and control groups, respectively, and the median survival was 20 months for both groups. Hematologic, gastrointestinal (GI), and infection-related complications were significantly more frequent and severe in the group treated with high-dose chemotherapy. Stomatitis, diarrhea, and skin toxicity were dose-limiting. However, there were no treatment-related deaths. High-dose induction combination chemotherapy with the agents used in this study failed to increase the response rate or survival duration, and resulted in a substantial increase in toxicity.

Adult↗

Percutaneous hepatic arterial infusion of cisplatin for metastatic breast cancer.

We treated 31 patients with breast cancer metastatic to the liver and refractory to prior chemotherapy with percutaneous hepatic arterial infusion of cisplatin (DDP) (120 mg/m2) at 4-week intervals. Partial responses occurred in five of 26 evaluable patients, with a median time to disease progression of 15+ weeks (range, 8+ to 55) and a median duration of survival of 11 months (range, 8-22). Toxic effects were acceptable and, except for catheter-related complications, were essentially similar to those encountered when DDP was given iv. Percutaneous hepatic arterial infusion of DDP has modest activity in the treatment of breast cancer metastatic to the liver.

Adult↗

A comparative study of bisantrene given by two dose schedules in patients with metastatic breast cancer.

Schedule dependency of bisantrene was evaluated in refractory metastatic breast cancer. Patients were randomly assigned to receive either a single (S) bolus injection of 300 mg/m2 (37 patients) or an injection of 80 mg/m2 daily for 5 days (D x 5) (35 patients) every 3-4 weeks after stratification by performance status, dominant disease site, and response to prior doxorubicin therapy. All but one patient had received prior doxorubicin. Partial remission (PR) was achieved by 5 of 35 patients (14%) in the S arm and 7 of 35 patients (20%) in the D X 5 arm (P = NS). There were 4 patients who had primary refractoriness to doxorubicin but responded to bisantrene. The median number of courses was two for both arms. The median time to progression was 5 months for the responders in each arm and 3 and 4 months, respectively, for patients who showed no change in the S and D X 5 arms. Myelo-suppression was dose-limiting and greater for the D X 5 arm. Drug fever (34% versus 21% of courses; P = 0.02) and myalgia (22% versus 10% of courses; P = 0.02) were reported more often in the D X 5 arm; malaise was greater in the S arm. Grade 2-3 nausea and vomiting occurred more often in the S arm (40% versus 10% of courses; P less than 0.01). Significant hypotension that was not symptomatic occurred in 1 patient in the D X 5 arm. Phlebitis occurred in 3 patients without a central line. One patient who had previously received doxorubicin and mitomycin C developed heart failure, which was controlled with medication. Bisantrene is an effective drug for metastatic breast cancer that has incomplete cross resistance to doxorubicin, and there was no schedule dependency in this study.

Adult↗

A comparative study of PALA, PALA plus 5-FU, and 5-FU in advanced breast cancer.

Sixty-three patients with Stage IV breast carcinoma refractory to standard combination chemotherapy agents such as 5-fluorouracil (5-FU) were entered into a study to determine the efficacy of a multiple dose schedule of N-(phosphonacetyl)-L-aspartic acid (PALA) and whether the addition of PALA improves the therapeutic efficacy of 5-FU. Patients were randomized to receive either PALA, 800 to 1000 mg/m2 per day for 5 days every 2 weeks; or PALA + 5-FU, 400 mg/m2 per day for 5 days, and 300 mg/m2 per day for 5 days every 28 days, respectively. The PALA alone arm of the study was closed after 20 patients had been treated and was replaced by 5-FU, 300 to 400 mg/m2 per day for 5 days every 21 days. Overall response rates were 5% for PALA alone, 28% for PALA + 5-FU, and 14% for 5-FU alone. All patients who responded to PALA + 5-FU or 5-FU alone had received prior therapy in which 5-FU was part of the combination chemotherapy program and were considered refractory to this drug. Toxicity affected the gastrointestinal tract but was tolerable in all three arms of the study. Myelosuppression was negligible for PALA and PALA + 5-FU and moderate for 5-FU. The authors concluded that PALA + 5-FU was superior to PALA alone in the therapy of these heavily pretreated patients. PALA alone had marginal efficacy. In view of its low hematologic toxicity, PALA + 5-FU may be combined with more myelosuppressive drugs. Additional studies are necessary to ascertain whether PALA + 5-FU is therapeutically superior to a full-dose schedule of 5-FU.

Adult↗

Five-day continuous-infusion vinblastine in the treatment of breast cancer.

One hundred six evaluable patients with metastatic breast cancer refractory to prior chemotherapy were treated with 5-day intravenous infusions of vinblastine at 1.4 to 2.0 mg/m2/day, through silastic elastomer permanent central venous catheters. Thirty-nine patients achieved objective responses; 5 were considered complete. The overall response rate of 37% was independent of prior exposure to intermittent intravenous vinca alkaloids or prior response to front-line doxorubicin combination chemotherapy. Objective responses were documented in 48% of the patients who received daily doses above 1.7 mg/m2 and in 32% and 29% of those treated with 1.7 mg/m2 or less, respectively (P = 0.10). Myelosuppression was more severe in responders, who received higher average doses, (median average nadir, 850 granulocytes/mm3) than in nonresponders (median, 1300 granulocytes/mm3), but was always rapidly reversible. Infections related to neutropenia were uncommon. Catheter-related toxicities occurred in 13 of 106 patients. Other toxicities were limited. These results confirm that vinblastine given as a continuous 5-day infusion is one of the most effective agents in the treatment of metastatic breast cancer and suggest that its activity is dose-dependent.

Adult↗

Oral medroxyprogesterone acetate in the treatment of metastatic breast cancer.

Thirty-nine evaluable, postmenopausal patients with metastatic breast carcinoma were treated with medroxyprogesterone acetate administered orally at daily doses of 800 mg/day in 29 patients and 400 mg/day in 10 patients. One patient experienced a complete remission and 16 had partial remissions for an objective remission rate of 44%. There was no apparent difference in response between the two dose levels. Median remission duration was 8 months, and median survival for the whole group is expected to exceed 18 months. Increased appetite (66%) and weight gain (97%) were the most common side effects, followed by fluid retention, muscle cramps, and increased blood pressure. Performance status improved and white blood cell and platelet counts increased in the majority of patients. Medroxyprogesterone acetate is an effective hormonal agent in the treatment of metastatic breast cancer.

Administration, Oral↗

Adriamycin, dibromodulcitol, and mitomycin combination chemotherapy for patients with metastatic breast carcinoma previously treated with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone.

Twenty-six evaluable patients with metastatic breast carcinoma previously treated with a combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) were treated with a combination of doxorubicin (Adriamycin), dibromodulcitol, and mitomycin (ADM). Four patients (15%) achieved complete remission, and 10 patients (39%) had a partial response. Five patients (19%) had stable disease, and seven patients (27%) experienced disease progression. The median time to disease progression was 10 months for responding patients (range, 4-44 months) and 5 months (range, 2-13 months) for patients with stable disease. The median survival duration was 15 months (range, 6-44+ months) for responders, 11 months (range, 2-27 months) for patients with stable disease, and 4 months (range, 2-41 months) for nonresponders. Two of the four patients with complete remission are alive and in continued remission at a follow-up of 44 and 40 months. Seventy-one patients with greater than or equal to two sites of metastasis responded, whereas 23% of patients with greater than or equal to three metastatic sites responded. Although higher responses were seen with soft tissue and osseous metastasis, responses were observed in all three sites of metastasis. This combination chemotherapy regimen with ADM is an effective second-line program for patients who have previously received CMFVP chemotherapy.

Adult↗

Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guerin and with or without irradiation in operable breast cancer. A prospective randomized trial.

Between May 1977 and April 1980, 238 patients with operable breast cancer were treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy. All patients were randomized to receive FAC alone or FAC with nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) vaccine. A randomization for routine postoperative irradiation was included in the study in May 1978. At the median follow-up of 33 months, 53 patients had developed recurrent disease. Up to the present time, there have been no significant differences in the disease-free survival of patients treated with FAC alone from those treated with FAC + BCG (P = 0.21). The disease-free survival for patients treated with and without routine postoperative irradiation was similar (P = 0.99). Disease-free survival of premenopausal and postmenopausal women was similar. The overall estimate of disease-free survival was 72% at 3 years.

Antineoplastic Combined Chemotherapy Protocols↗

Carminomycin. A new anthracycline analog in the treatment of advanced breast cancer.

Twenty-two patients who had metastatic breast cancer previously treated with combination chemotherapy, cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CMF with vincristine and prednisone, were treated with Carminomycin (carubicin) 20 mg/m2 body surface area by intravenous bolus injection once every 3 weeks. Of 21 evaluable patients, 1 patient achieved complete remission, 5 patients achieved partial responses, and 11 remained stable. Cases of acute drug toxicity included myelosuppression, phlebitis, and gastrointestinal symptoms; there were four cases of mild alopecia, which consisted of thinning of the scalp hair. There were three cases of biopsy-proven cardiomyopathy, contrary to previous reports from the United Soviet Socialist Republic, which indicated that this drug was relatively free of cardiotoxicity. The median duration of remission for responders was 23 weeks. It is believed that Carminomycin has significant activity against metastatic breast cancer and, because its side effects, especially nausea, vomiting, and alopecia, were considerably milder than those experienced with Adriamycin, further investigation of this drug is warranted.

Adult↗

Combination chemotherapy for metastatic breast cancer with fluorouracil, adriamycin, cyclophosphamide, and methotrexate.

Twenty-nine patients with metastatic breast cancer were treated with fluorouracil, adriamycin, cyclophosphamide (FAC), and methotrexate (MTX), with or without leukovorin rescue. Of 24 evaluable patients, one achieved a complete remission and 17 had partial responses. The overall objective response rate was 75%. The median survival from initiation of chemotherapy for the responding patients was 18 months. Four patients (17%) with stable disease had a median survival of 25 months. The addition of MTX to FAC chemotherapy did not improve the therapeutic efficacy of this combination; it did, however, increase the overall toxicity, especially the infectious complications when compared to FAC alone.

Alopecia↗